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Notes: Previous anatomical investigations have reported a direct projection from substantia nigra pars lateralis to the dorsal midbrain anticonvulsant zone. The present study tested the hypothesis that the anticonvulsant properties of nigral inhibition previously attributed to substantia nigra pars reticulata were, in fact, due to the suppression of neural activity in the adjacent pars lateralis. Using the electroshock model of epilepsy, a systematic map of the anticonvulsant effects of bilateral injections of muscimol (60 ng/0.5 μI per side) into different parts of substantia nigra was constructed. Electroshock (1 s of 40 mA 50 Hz AC) was administered via ear-clip electrodes 5 or 60 min following injections of muscimol, or 60 min after control injections of saline. To provide insight into the functional mechanisms whereby nigral inhibition might suppress tonic seizures the behavioural effects elicited by muscimol were also noted. No evidence supporting the experimental prediction was found. The most sensitive region of substantia nigra for suppressing tonic hindlimb extension was caudal pars reticulata. These data indicate a serious mismatch between the results of microinjection mapping studies and underlying patterns of anatomical connectivity. The behavioural reaction most closely associated with tonic seizure suppression was stereotyped locomotion; both were obtained maximally from caudal pars reticulata. Rostral substantia nigra was associated more with oral stereotypy, while a raised head position was observed at lateral injection sites and a lowered positioning of the head at medial locations. These data suggest that the rat substantia nigra may contain a functional organization based on a form of somatomotor topography. This organization may influence which part of the substantia nigra is most effective in suppressing seizures expressed by different muscle groups of the body.

Notes: Previous experimental work has established that activation of sites in the dorsal midbrain can suppress tonic hindlimb extension in the electroshock model of epilepsy. The most sensitive region for this effect is centred on the intercollicular area and is referred to as the dorsal midbrain anticonvulsant zone (DMAZ). Subsequent experiments have shown that the ipsilateral descending projection from this region to the ventrolateral pons is critically involved in mediating its tonic seizure-suppressing properties. The purpose of the present investigation was to test whether direct anticonvulsant effects in the electroshock model could be obtained from selective manipulation of DMAZ target regions in the ventrolateral pons. Animals were prepared with chronically implanted guide cannulae through which microinjections could be made directly into the lateral pontine reticular formation. Animals received injections of saline or bicuculline (25–200 pmol) administered either bilaterally or unilaterally. The effects of these injections on the animals' behaviour were determined in an open arena, after which maximal electroshock (1s, 40 mA, 50 Hz AC) was administered via ear-clip electrodes and the duration of tonic hindlimb extension was recorded. Bilateral injections of bicuculline (100 pmol) suppressed tonic seizures at a significantly higher proportion of sites centred on DMAZ target regions of the ventrolateral pons than surrounding areas. For injections centred on this region the suppressive effects of bicuculline were dose-related in the range 25–100 pmol. Unilateral injections of bicuculline into the ventrolateral pons also effectively suppressed tonic seizures in the electroshock model. Within the ventral pons there was a significant association between the behavioural and anticonvulsant effects of bicuculline; injections suppressing tonic seizures were associated with the induction of fast continuous locomotor activity, These data confirm that the DMAZ recipient region of the ventrolateral pontine reticular formation is part of a circuit which can suppress the manifestation of tonic hindlimb extension in the electroshock model. Whether this property is related to the participation of this region in normal locomotion and posture remains to be determined.

Notes: Pharmacological manipulation of the ventrolateral pontine reticular formation (vlPRF) of rats has an anticonvulsant effect in the maximal electroshock model of epilepsy. This study presents three anatomical experiments that determine the efferent projections from this region likely to mediate this anticonvulsant effect. In the first, the anterograde tracer biotinylated dextran amine (BDA) was injected into the vlPRF. A strong projection to the ventromedial medullary reticular formation (vmMRF) was revealed which continued only weakly to the spinal cord. In the second experiment, double-label procedures were used to indicate whether the BDA-labelled terminals from the vlPRF make contacts with neurons in vmMRF, retrogradely labelled with cholera-toxin B subunit from the lumbar spinal cord. Sections of the vmMRF were examined by: (i) light microscopy which showed significant overlap between terminals from vlPRF and retrogradely-labelled reticulospinal cells; (ii) confocal microscopy which showed labelled terminals in close association with reticulospinal cell bodies; and (iii) electron microscopy which showed vlPRF terminals making synaptic contact with reticulospinal neurons. Finally, immunohistochemical procedures in combination with anterograde tracing revealed that significant numbers of terminals labelled from vlPRF were also positive for markers of glutamatergic or GABAergic neurotransmission. This suggests that the projection from the vlPRF to the vmMRF is likely to include several different functional components. These connections could represent a final critical link of an anticonvulsant circuit that originates in the dorsal midbrain and projects via relays in the vlPRF and the vmMRF to interact with the low-level motor circuitry in the spinal cord.

Notes: Large neurons in laminae III and IV of the spinal cord which express the neurokinin 1 receptor and have dendrites that enter the superficial laminae are a major target for substance P (SP)-containing (nociceptive) primary afferents. Although some of these neurons project to the thalamus, we know little about other possible projection targets. The main aim of this study was to determine whether all cells of this type are projection neurons and to provide information about brainstem sites to which they project. Injections of cholera toxin B subunit were made into four brainstem areas that receive input from the spinal cord, and the proportion of cells of this type in the L4 spinal segment that were retrogradely labelled was determined in each case. The results suggest that most of these cells (〉90%) project to the contralateral lateral reticular nucleus (or to a nearby region), while many (〉60%) send axons to the lateral parabrachial area and some to the dorsal part of the caudal medulla. However, few of these cells project to the periaqueductal grey matter. As lamina I neurons with the neurokinin 1 receptor appear to be important in the generation of hyperalgesia, we also examined projection neurons in this lamina and found that for each injection site the great majority possessed the receptor. These results demonstrate that dorsal horn neurons which express the neurokinin 1 receptor contribute to several ascending pathways that are thought to be important in pain mechanisms.